Is CLGN p.Ile17Met (c.51T>G) pathogenic?

CLGN p.Ile17Met (c.51T>G) is classified Uncertain significance in CLGN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.0733); Absent from gnomAD v4.1.

How common is CLGN p.Ile17Met (c.51T>G) in the general population?

CLGN p.Ile17Met (c.51T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLGN p.Ile17Met (c.51T>G)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

CLGN p.Ile17Met

c.51T>G · rs2546268401 · VCV2604309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -1.6
Regional constraint	o/e 0.90	unconstrained · MANE · 24 kb · p 0.01 · regional, not allelic
Overall
CADD	6.779	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLGN
Protein: p.Ile17Met
Coding: c.51T>G
MANE Select: NM_004362
dbSNP: rs2546268401
Type: single nucleotide variant
Location: chr4:140413028 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.36

Full CLGN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLGN p.Ala210Thr Uncertain significance ★ ⚠ same type
CLGN p.Ala529Thr Uncertain significance ★ ⚠ same type
CLGN p.Ala63Gly Uncertain significance ★ ⚠ same type
CLGN p.Arg196Gly Uncertain significance ★ ⚠ same type
CLGN p.Arg373Ser Uncertain significance ★ ⚠ same type
CLGN p.Arg603His Uncertain significance ★ ⚠ same type
CLGN p.Arg608Gln Uncertain significance ★ ⚠ same type
CLGN p.Arg70Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/clgn-p-ile17met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown